In 2013, etherna went all in on a big idea: develop RNA-based therapeutics in an era when lipid nanoparticles (LNPs) were barely a footnote in drug development.
At the time, the industry was still relying on naked RNA, unprotected and vulnerable to degradation, as the go-to delivery method. Etherna’s initial approach focused on ex vivo treatments, engineering cells outside the body before reinfusing them into patients.
Early work in melanoma immunotherapy using TriMix RNA showed promise, but the challenges of scaling ex vivo therapies, combined with limited market enthusiasm, made it clear that the company needed to rethink its delivery strategy. “Even today, people are split between ex vivo and in vivo approaches,” says Bernard Sagaert, CEO of etherna. “But at the time, it was clear that for us to succeed, we needed a better delivery mechanism.”
Etherna turned its focus to direct intranodal injections, testing whether RNA could be administered directly to the immune system. The approach showed strong results in non-melanoma skin cancer, paving the way for a clinical trial in 2017, one that was ultimately cut short by the COVID-19 pandemic.
But the disruption also presented an opportunity. By this time, etherna had already begun investing in LNP-based delivery and had started developing its own lipid library.
In 2022, the company took a decisive turn, and what emerged was a different kind of company — one that didn’t stop at RNA manufacturing but went above and beyond to fix the weaknesses in how it’s designed, delivered, and produced.
The pivot
While etherna worked on its RNA drug development, it also began exploring LNP technology to improve delivery. At first, the company relied on licensed ionizable lipids, but this came with limitations. With a fragmented supply chain and increasing competition, etherna developed its own ionizable lipid library in collaboration with academic partners.
Then, in 2022, the company took a bold step. Key investors together with management redirected the business, “We made the decision not to focus on the clinic or do therapeutics anymore. Instead, we would focus on delivering cutting-edge enabling technologies and high-value services to advance drug development,” recounts Sagaert.
Instead of pushing its own drug candidates, etherna pivoted into a pure technology company, offering RNA quality optimization, LNP design, and scalable manufacturing solutions to partners. Sagaert, who had been with the company since 2017 as COO focusing on manufacturing, was named CEO to lead this transformation.
Rethinking RNA manufacturing
Even before etherna’s shift away from therapeutics, Sagaert had recognized a fundamental issue: RNA manufacturing remained stuck in an academic mindset. The processes used to produce mRNA were basic and inefficient, and much of the industry’s early upscaling efforts were built on these unoptimized methods. “The way RNA was produced was really still academic, very basic,” Sagaert explains. “And those were the systems that got upscaled for the COVID vaccines. But we’ve focused on product quality.”
Etherna now refines every stage of the RNA manufacturing process, solving key industry bottlenecks:
- RNA purity and scalability – Etherna has improved the purity of its RNA, optimizing untranslated regions (UTRs) to enhance expression levels. “Improving UTRs can give a tenfold increase in expression,” Sagaert says. “That means reducing the dose tenfold, which immediately cuts costs.”
- Reducing double-stranded RNA (dsRNA) – High levels of dsRNA impurities are a known issue in mRNA therapeutics, triggering unwanted immune responses. “We’ve reduced double-stranded RNA to extremely low levels and we’ve done it in the upstream IVT process, not downstream,” says Sagaert. “That means higher yields and lower costs without adding extra purification steps.”
- Batch consistency – etherna works on scalable, cost-effective RNA production, ensuring that each batch maintains purity and potency.
Fixing the weak links in LNPs
RNA optimization is only half the equation. Lipid nanoparticles (LNPs) are the industry standard for delivery, but etherna believes they still have significant flaws. “Most companies work on either RNA or LNPs,” says Sagaert. “But they don’t optimize them together. That’s a problem.”
Etherna has built an extensive library of 2,500 ionizable lipids, systematically testing their impact on delivery, biodistribution, and safety. The results speak for themselves. “We’ve done in vivo assays showing a five- to tenfold increase in expression compared to ALC-0315 and SM-102,” says Sagaert, referring to the lipids used in approved mRNA COVID-19 vaccines. “Better targeting, better safety, better distribution.”
The company now has six LNP platforms, each tailored for specific applications: prophylactic vaccination, liver disease treatments, intratumoral cancer immunotherapy, and autoimmune modulation. Some of these platforms have already been tested in non-human primates, while others remain in earlier preclinical development. Etherna’s focus is balancing potency, safety, and degradation, ensuring that each LNP platform is optimized for its specific therapeutic need.
Not a CDMO
Etherna rejects the CDMO label. While it offers contract services, the company positions itself as a technology-first partner, integrating R&D, process development, and regulatory expertise to advance RNA-based medicines. “We’re not a CDMO,” Sagaert emphasizes. “We reinvest everything into R&D. This is real innovation, not just manufacturing.”
Etherna’s end-to-end capabilities include:
- RNA design & sequence optimization
- LNP formulation & lipid engineering
- Scalable CMC process development
- Preclinical pharmacology & toxicology support
- Regulatory strategy & clinical development insights
The company’s experience as a former RNA drug developer gives it a unique edge — it understands not just how to make RNA, but how to make it work in real-world applications.
Going steady
Etherna’s expertise has led to key partnerships, including collaborations with Almirall and Dropshot. With Almirall, etherna is developing a dermatology treatment using its LNP platform. “A year ago, we had a starting point,” Sagaert says.
“Since then, we have leveraged etherna’s innovative proprietary mRNA capabilities and LNP formulations with Almirall’s leading expertise in medical dermatology to accelerate discovery of novel treatment options.”
The Dropshot collaboration is focused on early-stage cardiac and renal therapeutics. “It builds on Dropshot’s prior evaluation of etherna’s mRNA and LNP platforms,” says Sagaert.
Raising the bar for RNA
Despite the success of mRNA vaccines, the RNA field is still in its infancy — and etherna believes much of the current technology remains underdeveloped.
“There’s this assumption that, because COVID vaccines worked, the science is settled. It’s not,” Sagaert says. “We’re still figuring out quality control, optimizing LNPs, and making manufacturing more consistent.”
By integrating RNA quality, LNP technology, and scalable manufacturing, etherna is pushing RNA therapeutics beyond where they stand today. “Bringing RNA to market isn’t just about speed,” Sagaert says. “It’s about getting it right from the start.”
